Abstract
The role of K+ channels on the presser effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood- perfused dog lungs when vascular tone was elevated with U-46619: 1) 10-6 M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca2+-dependent K+ channels; and 3) 10-4 M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10-8 M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4- aminopyridine at elevated vascular tone significantly potentiated the presser effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca2+dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca2+-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 91-98 |
| Number of pages | 8 |
| Journal | Journal of Applied Physiology |
| Volume | 80 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 1996 |
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Keywords
- glibenclamide
- pulmonary capillary pressure
- pulmonary vascular compliance
- pulmonary vascular resistance
- tetraethylammonium ions
- vasoconstriction
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
Cite this
Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone is modulated by potassium channels. / Barman, Scott A.
In: Journal of Applied Physiology, Vol. 80, No. 1, 01.01.1996, p. 91-98.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone is modulated by potassium channels
AU - Barman, Scott A
PY - 1996/1/1
Y1 - 1996/1/1
N2 - The role of K+ channels on the presser effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood- perfused dog lungs when vascular tone was elevated with U-46619: 1) 10-6 M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca2+-dependent K+ channels; and 3) 10-4 M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10-8 M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4- aminopyridine at elevated vascular tone significantly potentiated the presser effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca2+dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca2+-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.
AB - The role of K+ channels on the presser effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood- perfused dog lungs when vascular tone was elevated with U-46619: 1) 10-6 M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca2+-dependent K+ channels; and 3) 10-4 M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10-8 M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4- aminopyridine at elevated vascular tone significantly potentiated the presser effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca2+dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca2+-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.
KW - glibenclamide
KW - pulmonary capillary pressure
KW - pulmonary vascular compliance
KW - pulmonary vascular resistance
KW - tetraethylammonium ions
KW - vasoconstriction
UR - http://www.scopus.com/inward/record.url?scp=0030069329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030069329&partnerID=8YFLogxK
U2 - 10.1152/jappl.1996.80.1.91
DO - 10.1152/jappl.1996.80.1.91
M3 - Article
C2 - 8847337
AN - SCOPUS:0030069329
VL - 80
SP - 91
EP - 98
JO - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
JF - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
SN - 8750-7587
IS - 1
ER -